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Basic Science > Bone metabolism > Flashcards

Bone metabolism Flashcards

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1
Q

Where is calcium in the body?

A
  • 99% sequested in bone
  • 1% in extracellular fluid
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2
Q

What is calcium important for ?

A
  • Bones
  • nerve
  • muscle
  • hormone function
  • clotting
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3
Q
A
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4
Q

what is plasma calcium found as?

A
  • 50% bound to albumin
  • 50% free
  • maintained at level 2.2-2.6mmol/L
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5
Q

Where is the calcium absorbed from?

A
  • The dudodenum
  • by active transport
  • mediated by calcium- binding protein and ATP
  • regulated by 1,25 dihydroxycholcalciferol (1,25 (OH)2- vitamin D3 via passive diffusion by the jejunum
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6
Q

What precentage of calcium filtered by kidneys is reabsorbed?

where does this occur?

A
  • 99%
  • 60% in proximal convoluted tubules
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7
Q

Where is phosphate found?

A
  • 85% stored in bone
  • functions as metabolite and buffer in enzyme systems
  • circulates unbound in plasma
  • daily requirement is 1-1.5g/day
  • dietary intake is usually sufficient
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8
Q

What is the recommended intake of calcium for children/ 10-25 yrs, 25-65yrs, lacation, post menopause females?

A
  • CHildren 600 mg/day
  • 10-25 yrs 1400 mg/day
  • 25-65 yrs 750 mg/day
  • lactation 2000 mg/day
  • post menopausal female 1500 mg/day
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9
Q

How is vitamin D obtained?

what is its role?

A
  1. Naturally occuring steriods are ingested from fish oils and plants
  2. activated by skin by UV light
  • they enhance calcium and phosphorous absorption across the small intestine via promotion and synthesis of calcium transporting protein and enhance osteoclastic resorption from bone , increasing serum **levels of calcium and phosphate **
  • vitamin D also inhibits PTH
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10
Q

How does the activation process of vitamin D occur?

A
  • UV light-> transforms 7 dehydrocholestrol to cholecalciferol ( vitamin D3)
  • hydroxylated in liver -> 25 hydroxycholecalciferol ( 25(OH) vitamin D3)
  • serum 25 hydroxycholecalciferol is the most accurate indicator of body vitamin D stores
  • further hydroxylation of 25 hydroxycholecalciferol occurs in mitochondria of proximal convulted tubular cells of kidney-> 1.25 dihydroxycholcalciferol ( 1.25(OH)2- vitamin D3- active form of vitamin D
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11
Q

What activated vitamin D metabolism?

A
  • Low serum calcium/ phosphate
  • High PTH
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12
Q

What happens to vitamin D when there is low levels of PTH or increased levels of CA/Po4?

A
  • Convserion of active 1,25 dihydroxycholecalciferol to inactive 24,25( OH)2 vitamin D3
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13
Q

What is parathyroid hormone?

A
  • 84 amino acid peptide
  • secreted by chief cells of the 4 parathyroid glands in the response to changes in EC calcium via calcium sensing receptor
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14
Q

When in PTH secreted?

A
  • In response to decreased serum calcium/phosphate
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15
Q

When is PTH inhibited by?

A
  • elevated serum calcium
  • elevated 1,25 dihydroxylcalciferiol
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16
Q

What is PTH actions in the kidney?

A
  • Stimulate of hydroxylation of 25 hydroxycalciferol 25(OH)- vitamin D3, in the proximal tubules-> indirect intestinal effects
  • increased reabsoption of filtered calcium in the kidney
  • promotion of urinary excretion of phosphate from kndney
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17
Q

What is PTH actions in the bone?

A
  • stimulates osteoclasts
  • stimulates precursors
  • -> bone reabsorption
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18
Q

What is PTH overall effect?

A
  • Serum calcium levels are increased and phosphate levels are decreased
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19
Q

What is calcitonin?

A
  • 32 aminoacid peptide
  • secreted by the parafollicular C cells of Thyroid gland
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20
Q

When is Calcitonin secreted?

A
  • In reponse to elevated serum calcium
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21
Q

When is calcitonin inhibited?

A
  • by decreased serum calcium
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22
Q

What does calcitonin do?

A
  • Directly inhibits osteoclasts ( have calcitonin receptors
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23
Q

What are calcitonin effects?

A
  • Include reduction of cellular motility
  • retraction of cytoplasmic extensions
  • reduction of ruffled osteoclast border
  • this produces a transient decrease in serum calcium
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24
Q

What is the effect of oestrogen?

A
  • Inhibits bone reasorption and therefore prevents bone loss
  • also inhibits bone formation
  • does not increase bone density
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25
Q

What is the effect of corticosteriods on bone?

A
  • Reduce GI absorption
  • increase renal excretion of calcium thus inhibiting bone matrix formation-> hyperparathyroidism-> rapid bone loss
  • pts on corticosteriods should be given calcium and vitamin D with or without bisphosphonates
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26
Q

What do thyroid hormones have on the bone?

A
  • Increase bone turnover
  • favouring bone absorption ( seen in hyperthyroidism)
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27
Q

What do growth hormones do to bone?

A
  • Produce a positive calcium balance by increasing gut absorption
28
Q

What does insulin do to bone loss?

A
  • Type i if poorly controlled may lead to bone loss
29
Q

What do growth factors IL1, IL6 TNF alpha, IGF & TGF do to bone loss?

A
  • IL1, IL-6 , TNF alpha stimulate proliferation of osteoclast precursors
  • IGF activates osteoblasts, produced by osteoblasts
  • TGF activates osteoblasts, also stimulates osteoclastic precursors in vitro
30
Q

What happens to bone mass with age?

A
  • Increases up to a peak between 16-25yrs
  • after this there is a normal phsyiological loss of bone mass over time for both men and women of 0.3-0.5 % per year
  • thus calcium balance is positive in the first decades of life after which it becomes negative
  • women have an increase in bone loss up to 2-3% at the menopause but after the first menopausal decade the rate of bone loss is equivalent for both men and women
31
Q

What is bone’s 3 main function?

A
  • primary reservoir of calcium
  • Haemopoietic marrow
    • located in cancellous bone supplies the body’s cells. tissues and organs with erythrocyte, leukocytes and platelets
  • Bone has a mechanical role in supporting the body’s tissues
32
Q

What is woven bone?

A
  • collagen fibres are aligned randomly
  • no lamellae-> bone weaker
  • more flexible
  • isotrophic characteristics- uniform properties in all directions
33
Q

Where is woven bone found?

A
  • Embryonic/ Neonatal skeleton
  • metaphyseal region of growing bones
  • fx callus of children
  • absent in normal adult but appears in hard callus following fx
  • also found in pathological fx- Pagets/osteogenesis imperfecta
34
Q

What forms cortical and cancellous bone?

A
  • Lamellar ( mature) bone
  • with stress orientated fibres
  • leads to an aniostrophic characteristic
35
Q

What cells lay down lamella bone?

A
  • Osteoblasts
36
Q

Within each lamella what do the collagen fibres do?

A
  • Run at oblique angles to each other- herring bone
  • Cement lines separate the lamella
37
Q

What is lamella bone composed of?

A
  • predominantly a matrix with a small population of osteocytes ( trapped osteoblasts) encased within bony lacunae and resting bone lining cells ( with osteoblastic potential) covering the bony surfaces
38
Q

Decribe cortical bone?

A
  • 80% of adult skeleton
  • lamella laid down in concentric rings-> tubular lamellar systems= osteons/Haversian systems
  • approx 50um diameter
  • individual osteons are aligned along lines of force (usually parallel with the long axis of the bone)
  • each osteon has a central haversian canal surrounded by 5-7 concentric rings of lamella
  • cement lines- separate osteons
39
Q

How do the osteocytes within the osteons communicate?

A
  • Via gap junctions within channels = canaliculi
40
Q

What is the name of the second set of canals that penetrate the cortical bone?

what is there function?

A
  • Volkmann’s canal
  • run perpendicular to the long bone axis connecting inner an outer surfaces of bone
  • canals carry blood vessels to and from the haversian system
41
Q

What is the young’s modulus of cortical bone?

A
  • YM 20GPa cf cancellous 1GPa
  • cortical bone is more resistant to bending and torsion
  • Denser
42
Q

Where is cancellous bone found?

A
  • metaphysis and epiphysis of long bones
  • centrally in cuboid bones
43
Q

What is the structure of cancellous bone?

A
  • 3d lattice of interconnecting tabeculae which are alignes along axis of mechanical stress, enclosing elements of the bone marrow
  • each of the trabeculae is made up of parallel sheets of lamella
  • osteocytes, lacunae adn canaculi similar to cortical bone
  • No haversian systems
  • x8 turnover rate of cortical bone due to large surface area
  • less dense, less elastic, brittle& less strong than cortical bone
44
Q

Describe the layers of the periosteum?

A
  • Inner cambial layer- loose, vascular , oseogenic
  • outer fibrous layer- more structural, less cellular and continuous with joint capsules
  • with age the periosteum thins adn has less osteogenic potential
45
Q

What is bone?

A
  • Composite materal consisting of cells 10% and matrix 90% that has inorganic and organic compotents
46
Q

Describe the cells of bone?

A
  • Osteoblasts
  • Osteocytes
  • Bone lining cells
  • Osteoclasts
47
Q

What are osteoblasts?

A
  • from Undifferentiated Mesenchymal stem cells in marrow
  • Produce osteoid ( bone forming cells) - contains type 1 collagen, deposied in pre-exisiting mineralised surfaces
  • Have great Synthetic capacity ( abundant rough endoplasmic reticulum, golgi apparatus and mitochondria)
  • show high alkaline phosphatase activity
  • mediated by bone morphogenic proteins,growth factors and cytokines
  • 3 fates
    • become inactive bone - lining cells
    • surround with matrix-> osteocytes
    • undergo apoptosis
48
Q

What are osteocytes?

A
  • osteoblasts that become entrapped by calcified bone matrix
  • 90% of bone cell population
  • interconnect via long cytoplasmic processes in the canaliculi
  • important in controlling calcium and phosphorous metabolism- respond to PTH/Calcitonin/ mechanical and electrical potential
49
Q

What are bone lining cells?

A
  • Flat cells lying on the surface of the bone possess cytoplasmic extensions that pentrate bone matrix & communicate with osteocytes
  • **Inactive osteoblasts **that may be reactivated to become osteoblasts
  • Gatekeeper function: when stimulated by PTH, they undergo cyclic adenosine monophosphate (cAMP) mediated morphological changes that expose the bone surface and allow osteoclasts to start resorption
50
Q

What are osteoclasts?

A
  • Mononuclear osteoclast precursor cells (preosteoclasts) arise from haematopoietic macrophage and monocyte stem-cell line
  • found in marrow and circulating blood
  • When stimulated these cells proliferate & fuse -> large multinucleated osteoclast
  • typically 3-20 nuclei, large no of mitochondria and lyosomes that produce acid phosphatase
  • osteoclasts reabsorb bone within pits = Howship’s lacunae on endosteal/periosteal surface of bone
  • Ruffles ( brush) border that increases surface area which binds to bone surface via Integrins, sealing the area
  • A low pH is produced beneath this area ( via carbonic anhydrase system, adenosine triphosphate dependent proton pumps and the Na/H+ exchange system which dissolves the inorganic apatite crystals
  • Acid protelytic lysosomal enzymes, such as tartrate-resistant isoenzyme of acid phosphatase ( TRAP) and cysteine proteinases such as cathepsin then hydrolyse the organic matrix components
  • In dense cortical bone, OC lead cutting cones that tunnel thru the bone creating resorption cavities
  • control of OC is related to OB
51
Q

What is a bone remodelling unit?

A
  • is an area of remodelling by a set of osteoblasts. osteoclasts and stromal supporting tissue
  • in normal bone formation matches resorption with continual turnover of bone
  • osteoclast precursors are activated -> osteoclasts which reabsorb bone
  • this is followed by reversal , whereby osteblast precursors are activated to form osteoblasts which lay down osteoid, which undergoes mineralisation to form bone
52
Q

What does the bone matrix consist of?

A
  • Inorganic matrix 60% - resists compression forces
  • Organic matrix 40% - resists tensile forces
53
Q

What is the inorganic matric composed of?

A
  • Calcium phosphate crystals analogous to calcium hydroxyapatite
  • Ca10 ( PO4)6(OH)2
  • Mineralisation-= formation of solid calcium phosphate crystals
  • Osteocalcium phosphate ( brushite)- also in bone
  • serves as reservoir 99% body’s calcium, 85% phosphorous, 40-60% Na/K
54
Q

What is the composition of the organic matrix?

A
  • Collagen type 1 =90% of organic matrix
  • triple helix of 2x alpha1 and 1x alpha2 chains with a repitive Gly XY sequence where glycine is the first position and X and Y are often proline/hydroxyproline arranged in a quarter staggered structural array-> single fibrils
  • responsible for the tensile strength of bone
  • small amount of V and XI collagen
  • Bone specific proteoglycans
    • invovled in mineralisation/organistion of collagen fibres/binding of growth factors
  • Non collagenous matrix proteins
    • Osteocalcin
    • Osteonectin
    • OSteopontin
    • bone sialoprotein II
  • ​Growth factors/cytokines
    • ​BMP-17 ( members of transforming growth factor beta)
    • Insulin growth factor I & II
    • Interleukins 1 &** 6**
55
Q

What is Osteocalcin?

A
  • produced by osteoblasts
  • involved in control of osteoclasts
  • gene on chromosome 1
56
Q

What is Osteonectin?

A
  • Secreted by Osteoblasts and platelets
  • regulation of mineralisation
  • gene on chromosome 5
57
Q

What is osteopontin?

A
  • A non bone specific cell- binding protein anchoring osteoclasts to mineralised matrix
  • gene on chromosome 4
58
Q

What is a good marker of bone turnover?

A
  • Hydroxyproline
59
Q

What is a good indiator of bone formation?

A
  • Pro-collagen
  • collagen telopeptides- carboxy-terminal
  • bone specific alkaline phosphatase
  • osteocalcin
60
Q

What is a good indicator of bone breakdown?

A
  • Pyridinoline and deoxypyridinoline
  • X linkages formation beween adjacent triple helices are broken down
61
Q

What is the blood supply to the bone?

A
  • Nutrient artery system- (high pressure )
  • Metaphyseal- epiphyseal system
  • Periosteal system ( low pressure)
62
Q

Describe the nutrient artery system?

A
  • Major artery enters the mid-diaphysis thru a nutrient foramen
  • once in medullary canal it divides into ascending and descending arteries or arterioles which anastomose with metaphsyeal vessels and directly penetrate the endosteal surface supplying the inner 2/3rd cortex
  • in a child these vessels end on the metaphyseal side of the physis, contributing to process of endochondrl ossification
  • at microscopic level, arterioles run in volkmann’s canals with branches to the haversian systems, draining to venules and then into central venous sinus and out via the nutrient vein
63
Q

Describe the metaphsyeal-epiphyseal system?

A
  • Periarticular system complex penetrates the thin cortex and supplies the metaphysis, physis and epiphysis.
  • the metaphyseal vessels anatomose with the medullary and epiphyseal arteries after the growth plate fusion
  • in epiphysis with large articular surfaces such as radial and femoral heads, vessels enter the bone between articular cartilage and the physis, making the supply tenuous
64
Q

Describe the periosteal system?

A
  • Capillaries enter at the sites of major muscle attachments, normally supplying outer 1/3rd of teh cortex
  • this is the domiant system in children- responsible for circumferential growth
    *
65
Q

what is the normal direction of blood fow in the bone?

A
  • Centrifugal
  • ie inside to out
66
Q

What happens to bone blood flow after IM nailing?

A
  • The endosteal blood suuply is damaged
  • the **periosteal system becomes dominant **
  • so the flow -> Centripetal = out to in
  • venous blood system is normally centripetal

Basic Science (31 decks)

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